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Biomedical subjects

R J Howard

Publications and source records attributed to R J Howard.

At least 145 records · Page 8Linked to original sources
PubMed1992

A national survey of surgeons' attitudes about patients with human immunodeficiency virus infections and acquired immunodeficiency syndrome.

We conducted a national survey to learn about surgeons' attitudes toward patients with human immunodeficiency virus infection and with acquired immunodeficiency syndrome. We received 1039 (72%) responses from 1451 potential respondents. Seventy-four percent (766 of 1028) of surgeons were in favor of routine human immunodeficiency virus testing of patients, yet only 6% did so routinely and another 6% did so selectively. Most (88%) surgeons believed that patients had a right to know if their surgeon was infected with the human immunodeficiency virus and would agree to be tested if so requested by a patient. Most (72%) surgeons also believed that surgeons with the human immunodeficiency virus should have their operating privileges restricted. Only 8% knew the risk of acquiring human immunodeficiency virus infection if they sustained a percutaneous injury with contaminated blood, and only 61% were familiar with the Centers for Disease Control guidelines on universal precautions. The respondents also believed that others were "making the rules" for them while they were "taking the risks."

Acquired Immunodeficiency Syndrome↗
PubMed1992

Mitral balloon valvuloplasty in pregnancy: advantages of a unique balloon.

The burden of pregnancy in patients with severe mitral stenosis continues to present a therapeutic challenge. We present two such cases successfully treated with balloon valvuloplasty using the Inoue balloon. The unique features of this balloon may render it the technique of choice for selected pregnant patients with severe mitral stenosis.

Adult↗
PubMed1992

The significance of choroid plexus cysts in fetuses at 18-20 weeks. An indication for amniocentesis?

Over a period of 25 months, all antenatal patients were offered a detailed ultrasound scan at 18-20 weeks' gestation. The lateral cerebral ventricles were scanned for the presence of choroid plexus cysts. Fifty-one patients found to have choroid plexus cysts were offered amniocentesis to exclude chromosomal abnormalities. One pregnancy, in which the only abnormality found was bilateral choroid plexus cysts, was terminated after trisomy 18 was detected on amniocentesis at 19 weeks. The other 50 pregnancies had normal fetal outcomes. The significance of the isolated finding of choroid plexus cysts is reviewed.

Adult↗
PubMed1992

The characterization of two monoclonal antibodies which react with high molecular weight antigens of asexual Plasmodium falciparum.

We prepared rat monoclonal antibodies (mAb) specific for very large Plasmodium falciparum proteins to assist in their characterization. Hybridomas prepared from rats immunized with parasitized erythrocyte (PE) proteins of greater than 200 kDa exhibited two patterns of Western blot reactivity with PE SDS extracts: one represented by clone 41E11 (IgM, kappa), the other by clone 12C11 (IgM, lambda). MAb 41E11 reacted by Western blotting with at least 15 antigens, most of which comigrated with antigens identified by the 33G2 human IgM mAb. The stage specificity of mAb 41E11 reactivity and indirect immunofluorescence (IFA) pattern closely resemble those previously described for antigens that share the EEXXEE sequence motif. Unlike mAb 33G2, MAb 41E11 immunoprecipitated a biosynthetically radiolabeled protein of 320 kDa. MAb 41E11 did not immunoprecipitate any cell surface 125I proteins. MAb 12C11 reacted on Western blotting with a different group of malarial antigens of approximately 44, 95, 117, 145, and 310 kDa, as well as with some low-molecular-weight, uninfected erythrocyte antigens. MAb 12C11 did not immunoprecipitate any cell surface 125I or biosynthetically labeled proteins. The 310-kDa antigen recognized by mAb 12C11 (denoted Ag 12A) does not correspond to PfEMP2 or the 320-kDa antigen recognized by mAbs 33G2 or 41E11. With trophozoites and more mature stages, fixed IFA reactivity of mAb 12C11 was at the parasite and in antigen aggregates in the host cell cytoplasm that extended to the PE plasma membrane. Indirect results suggest that Ag 12A does not correspond to cell surface-exposed PfEMP1 and is most likely a hitherto unidentified malarial protein.

Animals↗
PubMed1992

Binding of Plasmodium falciparum 175-kilodalton erythrocyte binding antigen and invasion of murine erythrocytes requires N-acetylneuraminic acid but not its O-acetylated form.

Sialic acid on human erythrocytes is involved in invasion by the human malaria parasite, Plasmodium falciparum. Mouse erythrocytes were used as a reagent to explore the question of whether erythrocyte sialic acid functions as a nonspecific negative charge or whether the sialic acid is a necessary structural part of the receptor for merozoites. Human erythrocytes contain N-acetylneuraminic acid (Neu5Ac), whereas mouse erythrocytes, which are also invaded by P. falciparum merozoites, contain 9-O-acetyl-N-acetylneuraminic acid (Neu5,9Ac2) and N-glycoloylneuraminic acid (Neu5Gc), in addition to Neu5Ac. We compared the effects of sialidase and influenza C virus esterase treatments of mouse erythrocytes on invasion and the binding of a 175-kDa P. falciparum protein (EBA-175), a sialic acid-dependent malaria ligand implicated in the invasion process. Sialidase-treated mouse erythrocytes were refractory to invasion by P. falciparum merozoites and failed to bind EBA-175. Influenza C virus esterase, which converts Neu5,9Ac2 to Neu5Ac, increased both invasion efficiency and EBA-175 binding to mouse erythrocytes. Thus, the parasite and EBA-175 discriminate between Neu5Ac and Neu5,9Ac2, that is, the C-9 acetyl group interferes with EBA-175 binding and invasion by P. falciparum merozoites. This indicates that sialic acid is part of a receptor for invasion.

Animals↗
PubMed1992

Trafficking of malarial proteins to the host cell cytoplasm and erythrocyte surface membrane involves multiple pathways.

During the asexual stage of malaria infection, the intracellular parasite exports membranes into the erythrocyte cytoplasm and lipids and proteins to the host cell membrane, essentially "transforming" the erythrocyte. To investigate lipid and protein trafficking pathways within Plasmodium falciparum-infected erythrocytes, synchronous cultures are temporally analyzed by confocal fluorescence imaging microscopy for the production, location and morphology of exported membranes (vesicles) and parasite proteins. Highly mobile vesicles are observed as early as 4 h postinvasion in the erythrocyte cytoplasm of infected erythrocytes incubated in vitro with C6-NBD-labeled phospholipids. These vesicles are most prevalent in the trophozoite stage. An immunofluorescence technique is developed to simultaneously determine the morphology and distribution of the fluorescent membranes and a number of parasite proteins within a single parasitized erythrocyte. Parasite proteins are visualized with FITC- or Texas red-labeled monoclonal antibodies. Double-label immunofluorescence reveals that of the five parasite antigens examined, only one was predominantly associated with membranes in the erythrocyte cytoplasm. Two other parasite antigens localized only in part to these vesicles, with the majority of the exported antigens present in lipid-free aggregates in the host cell cytoplasm. Another parasite antigen transported into the erythrocyte cytoplasm is localized exclusively in lipid-free aggregates. A parasite plasma membrane (PPM) and/or parasitophorous vacuolar membrane (PVM) antigen which is not exported always colocalizes with fluorescent lipids in the PPM/PVM. Visualization of two parasite proteins simultaneously using FITC- and Texas red-labeled 2 degrees antibodies reveals that some parasite proteins are constitutively transported in the same vesicles, whereas other are segregated before export. Of the four exported antigens, only one appears to cross the barriers of the PPM and PVM through membrane-mediated events, whereas the others are exported across the PPM/PVM to the host cell cytoplasm and surface membrane through lipid (vesicle)-independent pathways.

4-Chloro-7-nitrobenzofurazan↗
PubMed1992

Evaluation of indices of left ventricular contractility and relaxation in evolving canine experimental heart failure.

OBJECTIVE: The aim was to evaluate changes in indices of left ventricular contractility and relaxation in relation to changes in loading conditions in dogs with rapid pacing induced heart failure. METHODS: 14 conscious male mongrel dogs were paced at 250 beats.min-1 to severe heart failure, which occurred at 4.2(SD1.9) weeks. Six sham operated dogs served as controls. Right sided pressures were obtained by a thermodilution catheter. Left ventricular pressure and its derived variables were obtained by a high fidelity manometer tipped catheter. Rate corrected velocity of circumferential fibre shortening--end systolic wall stress relations were obtained by simultaneous haemodynamic and echocardiographic studies. RESULTS: In the paced dogs, baseline right atrial pressure, 6.4(2.0) mm Hg, and pulmonary capillary wedge pressure, 7.1(2.5) mm Hg, increased to 13.3(3.1) mm Hg and 34.5(7.1) mm Hg respectively at severe heart failure (both p less than 0.0001). The peak first derivative of left ventricular pressure dP/dt decreased from 1515(274) mm Hg.s-1 at baseline to 975(321) mm Hg.s-1 at severe heart failure (p less than 0.05) while baseline left ventricular end diastolic pressure, 4.4(3.7) mm Hg, and relaxation time constant tau, 18.0(4.5) ms, increased to 37.2(6.6) mm Hg (p less than 0.01) and 51.9(21.4) ms (p less than 0.05) respectively. The shortening-wall stress relation was markedly displaced downward from baseline. Furthermore, weekly studies revealed a major downward displacement of this relation by one week of pacing with no significant further shift at severe heart failure, whereas both end diastolic diameter (preload) and end systolic wall stress (afterload) increased significantly further from one week. In the sham operated dogs, there was no change over time in any of these study variables. CONCLUSIONS: In pacing induced heart failure, there is impairment of left ventricular contractility and relaxation. The major downward shift of the shortening-wall stress relation at one week suggests that left ventricular contractility is impaired early and may be the initiating mechanism of heart failure in this model.

Animals↗
PubMed1992

Hyperacute and acute kidney graft rejection due to antibodies against B cells.

Because of the perception of its uncertain clinical significance, the B cell crossmatch is not universally performed before renal transplantation. Even though sporadic cases of hyperacute rejection associated with B cell antibodies have been reported, doubts remain in light of other studies suggesting no effect on graft survival. This report describes 4 cases of graft rejection (3 hyperacute and 1 acute) that occurred in patients with anti-B-cell antibodies specific against donor HLA-DR or DQ antigens. Absence of anti-donor class I antibodies was confirmed in all cases by 2-color flow cytometry. Strong evidence for an antibody-mediated mechanism was found in one patient with anti-class I and anti-class II antibodies in serum transplanted with a class II mismatched kidney. In this case, only anti-class II antibodies were recovered in the eluate of the nephrectomy specimen. These four cases were compiled from three different institutions over a four-year period, which confirms the infrequent occurrence of these events. While anti-class II antibodies may not always be detrimental for graft survival, these results also confirm that they have the potential to cause hyperacute or acute graft loss. We conclude that the information provided by the B cell crossmatch should be available at the time that a decision to proceed with a renal transplant is made.

Adult↗
PubMed1992

Plasmodium falciparum-infected erythrocytes do not adhere well to C32 melanoma cells or CD36 unless rosettes with uninfected erythrocytes are first disrupted.

Plasmodium falciparum malaria parasites modify the human erythrocytes in which they grow so that some parasitized erythrocytes (PE) can cytoadhere (C+) to host vascular endothelial cells or adhere in rosettes (R+) to uninfected erythrocytes. These C+ and R+ adherence properties of PE appear to mediate much of the pathogenesis of severe malaria infections, in part by blocking blood flow in microvessels. From one parasite strain, PE were selected in vitro for C+ R+ or C+ R- adherence properties and examined in model adherence assays. The C+ R+ PE cytoadhered poorly to C32 melanoma cells or to immobilized CD36 in a settled-cell assay when uninfected human erythrocytes were present and formed rosettes with PE. C+ R- PE adhered well in the same assays. However, C+ R+ PE adhered very well, even better than C+ R- PE, when the rosettes were disrupted and the C+ R+ PE were purified. Adding back rabbit erythrocytes, which do not form rosettes with C+ R+ PE, had simply a dilutional effect. The ability of rosettes to interfere with the detection of adherence must be dealt with in all future assays of malarial PE adherence. Individual PE were observed attached simultaneously to C32 cells and to a few erythrocytes, suggesting that C+ and R+ adherence properties are coexpressed on the same PE. Coexpression of these adherence properties on the same PE may have pathological importance in vivo, where passage of rosettes through capillaries may shear uninfected erythrocytes from rosetted PE and allow direct PE attachment to postcapillary venule walls before rosettes reform.

Animals↗
PubMed1992

Plasmodium falciparum-infected erythrocyte receptor(s) for CD36 and thrombospondin are restricted to knobs on the erythrocyte surface.

Adherence of Plasmodium falciparum-infected RBCs (PRBC) to endothelial cells causes PRBC sequestration in cerebral microvessels and is considered to be a major contributor to the pathogenesis of cerebral malaria. Both CD36 and thrombospondin (TSP) are glycoproteins that mediate PRBC adherence to endothelial cells in vitro. Because they are both expressed on the surface of endothelial cells, they probably contribute to PRBC sequestration and vascular occlusion in vivo. By applying affinity labeling of receptor binding sites with purified ligands, we showed for the first time that both CD36 and TSP can bind independently to the PRBC surface and that the PRBC receptor(s) for CD36 and TSP are localized specifically to the electron-dense knob protrusions of the PRBC surface. These findings may help in efforts to develop a malaria vaccine to prevent cerebral malaria.

Affinity Labels↗
PubMed1992

Plasmodium coatneyi-infected rhesus monkeys: a primate model for human cerebral malaria.

Although several animal models for human cerebral malaria have been proposed in the past, none have shown pathological findings that are similar to those seen in humans. In order to develop an animal model for human cerebral malaria, we studied the pathology of brains of Plasmodium coatneyi (primate malaria parasite)-infected rhesus monkeys. Our study demonstrated parasitized erythrocyte (PRBC) sequestration and cytoadherence of knobs on PRBC to endothelial cells in cerebral microvessels of these monkeys. This is similar to the findings seen in human cerebral malaria. Cerebral microvessels with sequestered PRBC were shown by immunohistochemistry to possess CD36, TSP and ICAM-1. These proteins were not evident in cerebral microvessels of uninfected control monkeys. Our study indicates, for the first time, that rhesus monkeys infected with P. coatneyi can be used as a primate model to study human cerebral malaria.

Animals↗
PubMed1992

Purification and in vitro selection of rosette-positive (R+) and rosette-negative (R-) phenotypes of knob-positive Plasmodium falciparum parasites.

We have developed methods for in vitro selection of Plasmodium falciparum parasites that bear knob protrusions (K+) and are either of the rosette-positive (K+R+) or rosette-negative (K+R-) phenotypes. Cryopreserved parasites from spleen-intact Aotus monkeys that were K+, C32 cell adherence-positive (C+), CD36 adherence-positive, and R- with Aotus erythrocytes were adapted to continuous growth in human erythrocytes, and selected initially for adherence to C32 melanoma cells. In the absence of independent selection for rosettes, K+R-C+ parasites were produced that adhered to both C32 cells and CD36. Without selection for the C+ phenotype, K+R-C- parasites eventually predominated in such cultures. The R+ parasites were selected using differences in sedimentation behavior of rosette-infected cells versus non-rosette-infected cells. Methods were devised for selection of the R+ or R- phenotypes and for the purification of R+ or R- infected cells of high parasitemia that were suitable for molecular studies. With the repeated selection for K+R+ parasites, we were able to maintain the K+R+ phenotype for several months in vitro. These methods will allow systematic study of the molecular basis of the K+R+ and K+R- phenotypes.

Animals↗